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M Manfrini

Publications and source records attributed to M Manfrini.

At least 37 records · Page 2Linked to original sources

Predictive factors for local recurrence in osteosarcoma: 540 patients with extremity tumors followed for minimum 2.5 years after neoadjuvant chemotherapy.

We investigated predictive factors for local recurrence in 540 patients with non-metastatic osteosarcoma of the extremity treated with surgery and neoadjuvant chemotherapy, between March 1983 and October 1994. The median follow-up was 7.5 (2.5-15) years. Local recurrences developed in 31 (6%) patients after a median time of 2 (0.5-7) years. Local recurrence did not correlate with patients' age and sex, histologic subtype, site and tumor volume, presence of pathologic fracture, chemotherapy regimen and type of surgery. Local recurrence-free survival (LRFS) correlated with the quality of surgical margins and response to chemotherapy: the 7-year LRFS was 97% after adequate surgical margins and 71% after inadequate surgical margins (p < 0.0001), and was 95% in good responders and 90% in poor responders (p = 0.001). Only 1 of 31 patients with local recurrence was free of disease 15 months after the last treatment, 3 were alive with uncontrolled disease and 27 died. This post-relapse outcome is significantly worse than in patients who relapsed with metastases only (25% free of disease, 0.5-9 years after the last treatment). We conclude that, in osteosarcoma of the extremity, limb-salvage procedures should be planned only when the preoperative staging indicates that it is possible to achieve adequate surgical margins. If the pathologic examination of the surgical specimen shows inadequate surgical margins, an immediate amputation should be considered, especially if the histologic response to preoperative chemotherapy was poor.

Adolescent↗

Osteogenic sarcoma of the extremity with detectable lung metastases at presentation. Results of treatment of 23 patients with chemotherapy followed by simultaneous resection of primary and metastatic lesions.

BACKGROUND: In the past 20 years, it has been demonstrated that the combination of surgery and chemotherapy improves the prognosis for patients with osteosarcoma of the extremity without detectable metastases at presentation. By contrast, the efficacy of chemotherapy coupled with aggressive surgery has not yet been well established for patients with metastatic disease at diagnosis. The current study evaluates the efficacy of chemotherapy associated with simultaneous surgery of primary and metastatic lesions in patients presenting with osteosarcoma of the extremity with lung metastases. METHODS: Patients with lung metastases originating from an osteosarcoma of the extremity received chemotherapy (high dose methotrexate, cisplatin, doxorubicin, and ifosfamide) followed by simultaneous resection of primary and metastatic lesions and additional chemotherapy. RESULTS: Between January 1993 and June 1995, 23 patients entered the study. After primary chemotherapy, lung metastases disappeared in three patients, whereas in four patients they remained surgically unresectable. All seven patients received surgical treatment of the primary tumor only. In the remaining 16 patients, a simultaneous resection of the primary and metastatic tumors was performed after chemotherapy. The resection of metastatic lesions resulted in a complete remission in 15 patients and an incomplete remission in 1 patient. All five patients who never achieved tumor free status died within a few months. Of the 18 patients who achieved radiologic remission at a 30-month follow-up (range, 14-50 months), 10 (55.5%) remained continuously free of disease, 7 relapsed with new metastases, and 1 died of toxicity. In 13 of the 18 patients who underwent a complete simultaneous resection of the primary and the metastatic lesions, or whose pulmonary metastases disappeared after chemotherapy, a strong correlation was found between degree of necrosis of the primary tumor and of the metastatic tumor. CONCLUSIONS: In patients presenting with osteosarcoma of the extremity with lung metastases, the combination of aggressive chemotherapy with simultaneous resection of the primary and metastatic lesions improves traditionally negative outcomes. The strong correlation found between the histologic response of the primary and metastatic tumors supports the strategy, largely used currently in the neoadjuvant treatment of osteosarcoma, of tailoring postoperative chemotherapy on the basis of the histologic response of the primary tumor to preoperative chemotherapy.

Adolescent↗

Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing's sarcoma of the extremities.

PURPOSE: This study was performed to assess the prognostic value of the proposed histopathologic method to evaluate the response of the primary tumor to preoperative chemotherapy in Ewing's sarcoma. PATIENTS AND METHODS: The response to chemotherapy was evaluated from the specimens of 118 Ewing's sarcoma patients, who were preoperatively treated by chemotherapy alone. Responses were graded I to III (macroscopic viable tumor, microscopic viable tumor, and no viable tumor cells, respectively). Follow-up data were available for all patients, with a mean follow-up duration of 86 months (range, 30 to 158). RESULTS: A statistically highly significant difference was observed in outcome among the three groups of patients. For patients with total necrosis (grade III response), the estimated 5-year disease-free survival rate was 95%, in contrast to 68% for grade II responders and 34% for grade III responders (P < .0001). This difference was also confirmed when any single group was compared with the other groups. Among the parameters tested, patient age and the size of tumor had some prognostic value. CONCLUSION: The proposed histopathologic grading, to evaluate the effect of chemotherapy on the primary tumor, had the strongest correlation to clinical outcome. This method could therefore be used to identify patients with a high risk of recurrent disease. These patients could be randomized to receive alternative postoperative treatments to investigate whether more aggressive therapies will improve outcome.

Adolescent↗

[Traditional radiology in the assessment of posttraumatic carpal instability].

INTRODUCTION: Carpal instability is a painful posttraumatic syndrome with early or late loss of the normal alignment of the carpal bones, which can be caused by a variety of injuries, from minor sprain to major fracture-dislocation of the carpal-wrist complex. If the trauma causing instability is a fracture, a severe dislocation or a fracture-dislocation, the radiographic diagnosis is not particularly difficult. The morphologic and dynamic complexity of the carpal region represents, instead, a major obstacle in the radiologic diagnosis of mild or moderate sprains because the morphologic alterations on standard static views are minimal or absent in these conditions. MATERIALS AND METHODS: We reviewed 214 injuries causing posttraumatic carpal instability including both the cases classified by the Data Analysis Center of the Istituto Ortopedico Rizzoli as carpal dislocations and fracture-dislocations from January, 1975, to July, 1996, and the more recent cases directly observed at our Casualty Clinic. In the former cases, we reviewed only the available images, while our patients were examined with comparative standard and under stress or dynamic views. RESULTS: Of 214 lesions causing posttraumatic carpal instability, 43 along the great arch were classified as severe because they were easily detectable on standard films and 171 along the small arch were classified as mild because slight/no abnormalities were detected on standard static views. Only dynamic imaging showed posttraumatic carpal instability demonstrating the integrity of the ligaments and of the carpal hinges, as well as gaps or asymmetry not detected on static views. CONCLUSIONS: We suggest the systematic use of dynamic imaging in the cases where static findings are negative or poor, in the patients with a painful wrist after an apparently minor sprain. Missed or delayed diagnoses are thus reduced, as well as the consequent joint incongruity and/or chronic subluxation which may severely impair these patients.

Carpal Bones↗

Synchronous multifocal osteosarcoma: results in twelve patients treated with neoadjuvant chemotherapy and simultaneous resection of all involved bones.

BACKGROUND: Multifocal osteosarcoma is a rare type of tumor which is always excluded from therapy trials and is therefore rarely investigated for prognosis and treatment. PATIENTS AND METHODS: Twelve patients with synchronous multifocal osteosarcoma underwent neoadjuvant chemotherapy and, when feasible, simultaneous resection of involved bones. RESULTS: Four patients were unsuitable for resection and died 5-13 months (average 9 months) later. In eight patients all lesions were resected simultaneously. Four patients are disease-free at 15, 20, 24, and 60 months (average 29 months), and four relapsed and died at 12, 24, 30 and 36 months (average 30.5 months). CONCLUSIONS: Chemotherapy associated with aggressive surgery may be useful. The histological response of different lesions in the same patient are strongly correlated, confirming that synchronous multifocal osteosarcoma is not originally multicentric but unicentric with bone metastases.

Adolescent↗

Unicameral and aneurysmal bone cysts.

Unicameral and aneurysmal bone cysts are considered tumorlike conditions of unclear origin. The diagnosis of unicameral bone cysts is almost always based on the radiographic appearance, whereas aneurysmal bone cyst imaging may sometimes mimic a sarcomatous lesion. Several pathogenetic hypotheses [correction of hypothesis] reported in literature have been described. Classifications have been proposed to detect the activity of the cysts and to predict the prognostic behavior. The results observed with different options of treatment have been discussed.

Bone Cysts↗

[Neoadjuvant chemotherapy in malignant fibrous histiocytoma of the limbs: 10 years of experience (1983-1992) at the Rizzoli Orthopedic Institute].

During the period September 1983 to December 1991, 47 patients with nonmetastatic malignant fibrous histiocytoma (MFH) of the limbs were treated using 3 different protocols of neoadjuvant chemotherapy activated at successive intervals. Surgery consisted of limb salvage in 41 cases and amputation in 6. After a mean follow-up of 6.5 years 33 patients (70%) had been continuously disease-free and 14 had undergone relapses. In the latter group the first sign of recurrence was metastasis in 12 cases and local recurrence in 2 cases. These results are distinctly better than those obtained in 20 patients treated during the same period using surgery alone (24% of disease-free survival and 30% local recurrence), and compared to those obtained in an earlier study in which surgery was associated with postoperative chemotherapy alone (59% of disease-free survival and 25% of local recidivation). The authors conclude that, as already observed in the case of osteosarcoma, neoadjuvant chemotherapy can significantly improve prognosis even in patients with bone MFH localised in the limbs. Moreover, given that, contrary to adjuvant chemotherapy, associated chemotherapy is effective not only in controlling the microscopic disease but also reducing the incidence of local recurrence, it enables amputation to be avoided in the majority of patients.

Adult↗

Cellular schwannoma. A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients.

BACKGROUND: A clinicopathologic study of 70 cases of cellular schwannoma was performed to assess their distribution, response to therapy, and rate of recurrence relative to modern prognostic indicators. METHODS: Seventy-one cellular schwannomas from 70 patients were retrieved from the files of the Mayo Clinic Tissue Registry. The significance of mitotic index, proliferative marker staining (proliferating cell nuclear antigen and MIB1), immunochemical p53 expression, and DNA ploidy were assessed relative to tumor behavior, particularly recurrence. All parameters were subject to statistical analysis (Student's t test). RESULTS: Cellular schwannomas represented 4.6% of benign peripheral nerve tumors operated on at the Mayo Clinic. In 15% of the cases, an initial diagnosis of malignancy had been made. The median patient age was 47.7 years (range, 15-80 years) and the female-to-male ratio was 1.6:1. The principle tumor locations were the para- and intraspinal regions, including the sacrum (64%), extremities (25%), and intracranial space (8%). All tumors consisted primarily of hypercellular, compact, Antoni A tissue. Mitoses (< or = 4/10 hPF]) were observed in 71% of the cases. Foci of necrosis were noted in 11% of cases. Ultrastructural studies and immunohistochemistry clearly demonstrated features of schwannian differentiation. Surgery was the treatment in all cases. Excision was intralesional to gross total in the majority; total resection with wide margins was undertaken in three tumors, each of which had initially been considered malignant. Follow-up in 47 patients (67%) ranged from 1 to 29 years (mean, 7.7 years) and revealed recurrences in 11 patients (23.4%): no patient experienced metastasis or died of tumor. Although no correlation existed between recurrence and DNA ploidy, percent S-phase determinations, proliferation marker (PCNA, MIB1) staining, or the frequency of p53 immunoreactivity, a statistically significant correlation (P < 0.001) was observed, however, between recurrence and mitotic indices. CONCLUSION: Proliferation indices, as defined by immunochemical analysis, are not useful predictors of recurrence in cellular schwannoma. In lesions not completely resected, tumor recurrence is significantly correlated with mitotic count. The significant overall frequency of recurrence in this series is attributable to a high proportion of intraspinal and intracranial tumors. Our study confirms the benign nature of cellular schwannoma and underscores the necessity of distinguishing them from malignant peripheral nerve sheath tumors, lesions that often require adjuvant therapy.

Adolescent↗

[The epiphyseal involvement of metaphyseal bone sarcomas in patients with fertile growth plates. A magnetic resonance assessment].

The growth plate is thought to be capable of limiting tumor spread. To assess the presence and extent of epiphyseal involvement in bone tumors, the plain radiographs and the MR images of 41 patients with metaphyseal sarcoma and radiographically apparent growth plate were studied. The results were compared with surgical, microscopic and histologic findings. Histology demonstrated that in 3 patients the tumor did not reach the growth plate, in 25 the epiphysis was involved while in 13 cases the tumor reached the physis but did not spread to the epiphysis. In the latter group of patients, histology demonstrated a microinfiltration of the physis in 5 cases. Radiography and MR sensitivities were 77.2% and 100%, respectively, while specificity was 94% for both methods. Histology showed that the epiphysis was involved in 25/41 cases (61%) and the growth plate in 30/41 (73%). Our results show that the growth plate does not usually act as a barrier against tumor spread and that MRI is the diagnostic tool of choice in the assessment of epiphyseal spread in metaphyseal tumors even though it cannot detect growth plate microinfiltrations.

Adolescent↗

Effect of electromagnetic fields on patients undergoing massive bone graft following bone tumor resection. A double blind study.

Massive bone allograft after tumor resection has been used for over 20 years. Many factors negatively influence the healing of the junction between the allograft and the host bone, resulting in a low healing rate and lengthy time to union. This study evaluated whether pulsing electromagnetic field stimulation could be advantageously used in these patients. A double blind prospective randomized study was designed. Eighty three host graft junctions in 47 patients were considered. The overall host graft junction healing rate was the same (67%) in both control and active stimulated patients. Although not statistically significant, a positive effect of pulsing electromagnetic fields was observed for those host graft junctions with a cortico-cortical contact between allograft and host bone. When adjuvant postoperative chemotherapy was not employed, a definite effect of pulsing electromagnetic field stimulation was observed: the healing time decreased from 9.4 months in the control group to 6.7 months in the active stimulated group (p < 0.001). This effect would have been lost if chemotherapy was employed. There was also no advantage in supplement with iliac crest autografts at the host graft junction site if chemotherapy was used. Factors that significantly influenced the host graft junction healing rate were: chemotherapy; type of allograft host bone contact; quality of host graft junction; and, in intercalary allografts, use of the osteosynthesis device. No difference was observed between control and active groups for patient survival or number of local or distal tumor recurrences.

Adolescent↗

[Osteosarcoma: magnetic resonance imaging of the effects of preoperative chemotherapy].

The effects of preoperative chemotherapy for osteosarcoma of the extremities were investigated with MR imaging. Forty-six patients affected with high-grade osteosarcomas of the extremities underwent MRI before and after two cycles of preoperative chemotherapy. At the end of treatment all tumors were resected and the rate of tumor necrosis was assessed on histologic sections. The MR images obtained before and after treatment were compared. Decreased tumor size, perilesional intramedullary edema and more marked lesion outline correlated well with positive histologic response to preoperative chemotherapy. Soft tissue edema and joint effusion did not change significantly and no clear correlation with histologic response was observed. Decreased signal intensity on T2-weighted images is likely to indicate response to chemotherapy. Likewise, poor response correlated with unchanged/increased signal intensity. Therefore, MRI appears a useful means to evaluate chemotherapy-induced changes in osteosarcomas of the extremities.

Adolescent↗

Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.

Between September 1986 and December 1988, 125 patients with osteosarcoma of the extremities entered the second neoadjuvant study at the authors' institution. Patients received preoperatively two cycles of methotrexate (MTX) intravenously, followed by cisplatinum (CDP) intraarterially, plus adriamycin (ADM) intravenously. After surgery, the patients classified as "good responders" (more than 90% tumor necrosis) received ADM, MTX, and CDP, while the "poor responders" (less than 90% tumor necrosis) had a longer chemotherapy that included ifosfamide and etoposide (VP-16) in addition to MTX, ADM, and CDP. Limb salvage was possible in 85% of patients, 8% had an amputation, and 7% had a rotationplasty. The surgical margins were adequate (radical or wide) in 88% of cases and inadequate (marginal or intralesional) in 12%. At an average follow-up period of 28 months (range, 13 to 41), 109 patients (87%) remained continuously disease free, 15 (12%) relapsed with pulmonary metastases, and one patient (0.8%) had a local recurrence. Compared with the first neoadjuvant study at the authors' institution that used only MTX and CDP preoperatively, the percentage of limb salvages, "good responders," and continuously disease-free survival at two years was significantly higher in the second Rizzoli neoadjuvant study (85%, 74%, and 87% versus 77%, 52%, and 59%). Systemic toxicity because of chemotherapy was superimposable. A retrospective analysis of the real dose intensity for each patient demonstrated a correlation between the intensity of chemotherapy and prognosis.

Adolescent↗

The management of malignant bone tumors in children and adolescents.

A series of 205 pediatric patients affected by osteosarcoma, Ewing's sarcoma, fibrosarcoma, and malignant fibrous histiocytoma of bone were treated from 1978 to 1988. Ninety-eight percent of the patients received chemotherapy and 63% had a surgical resection. Sixty-five percent of all patients were alive at 30 months and were considered disease free. The functional results after surgery were evaluated according to the Musculoskeletal Tumor Society score. In all diaphyseal resections and resections of the upper extremity and pelvis, the results were excellent or good in 60% of the cases. In resections of the proximal femur, distal femur, or proximal tibia and reconstruction with nonexpansible prostheses, the results were excellent or good in 75%. On the other hand, when arthrodeses of the lower extremity were used, only 14% of cases had a good result. This correlates with the resulting lack of articulation and serious limb shortening seen with progression of skeletal growth.

Adolescent↗

Hemipelvectomy in malignant neoplasms of the hip region.

The authors report the results of 76 hemipelvectomies performed from 1978 to 1988 in malignant neoplasms of the hip region. Several surgical techniques were employed, including King and Steelquist's "classic" technique (77%), the technique involving the anterior flap of the thigh (9%), and the technique involving the subcutaneous gluteal flap (14%). In 8 cases palliative surgery was performed. Of the remaining 68 patients, 31 (45%) are alive and show no signs of the disease after an average of 44 months. Postoperative complications are discussed in relation to surgical technique and previous adjuvant therapy; the subcutaneous gluteal flap technique exposes the patient to the greatest risk of major complications (54%), while the "classic" technique is the most reliable, although there was superficial infection in 18% of cases. Fifty percent of the patients previously treated with radiotherapy suffered local postoperative complications. In order to reduce local recurrence, special care is advised in the preoperative stages and in the execution of the pelvic osteotomies.

Adolescent↗

[In vitro study of Staphylococcus epidermidis adhesiveness to suture materials].

In surgical divisions, where you can find the highest percentage of hospital infections, the surgical wounds are definitively the most frequent localization. The aim of our study was to evaluate whether bacterial-biomaterial interactions could influence the growth of infections in sutured tissues. We prepared a method for in vitro bacterial adhesiveness testing based on turbidimetric analysis. The results obtained show a different grade of bacterial adhesion in relation to physical and chemical characteristics of the material examined.

Bacterial Adhesion↗

Long-term results in 144 localized Ewing's sarcoma patients treated with combined therapy.

The results of 144 previously untreated cases of primary Ewing's sarcoma of bone are reported with a minimum follow-up of 5 years. This series was treated between 1972 and 1982 at Istituto Ortopedico Rizzoli with a combined therapy. The local control of the disease consisted of amputation (ten cases), resection followed by radiation therapy (35-45 Gy) (48 cases) and radiation therapy alone (40-60 Gy) (86 cases). Adjuvant chemotherapy, rigorously standardized, was performed according two different protocols: the first (85 cases treated in the period 1972-1978) consisted of vincristine (VCR) Adriamycin (doxorubicin) (ADM), and cyclophosphamide (EDX); the second (59 cases treated in the period 1979-1982) of VCR, ADM, EDX and dactinomycin (DACT). At a follow-up of 5 to 16 years (median, 9), 59 patients (41%) are continuously disease-free (CDF), 81 (56%) developed metastatic disease and/or local recurrence, and four (3%) had a second malignancy. Three factors seem to be correlated to prognosis: the site of the initial lesion (only 23% of the pelvic lesions are represented in the CDF group versus 46% of the other locations); the chemotherapy protocol (32% of the cases in the first protocol are CDF versus 54% in the second); the type of local treatment (60% of the patients treated with amputation or resection plus radiotherapy versus 28% of those treated with radiation therapy alone are CDF). A local recurrence was observed in 24% of the patients (8% in the group locally treated with surgery or surgery plus radiation therapy versus 36% in the group treated with radiation therapy alone). These data suggest that even though adjuvant chemotherapy can improve the long-term results in localized Ewing's sarcoma patients, this disease still represents, in a high percentage of cases, a lethal process whose final prognosis widely depends on the local control of the lesion. Due to the questionable effect of the radiation therapy alone in controlling the primary lesion and its important side effects, the role of surgery in treating Ewing's sarcoma of bone should be extended.

Adolescent↗

Post-injective quadriceps contracture.

After reviewing the literature, the authors report 19 patients affected with post-injective contracture of the quadriceps muscle observed by them between 1971 and 1983. Clinical evaluation, indications for surgery and the results of surgery are discussed.

Child↗